Background for Fast Fact #504: Systemic rheumatic diseases (SRDs) refer to autoimmune disorders that can affect multiple organ systems, like rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and inclusion body myositis. These diseases can contribute to a terminal process as a comorbid illness or be fatal themselves. The decision of whether to continue, stop, or switch disease-modifying anti-rheumatic drugs (DMARDs) for patients with SRDs at the end of life is complex. This Fast Fact will provide a brief overview of considerations relevant to determining the appropriateness of DMARDs at the end of life.

DMARDs for SRDs: DMARDs are commonly prescribed for SRDs to suppress the immune system and slow disease progression. They are categorized as conventional (methotrexate, hydroxychloroquine, sulfasalazine), biologic (adalimumab, infliximab, rituximab, belimumab, etanercept), and targeted synthetic (Upadacitinib, baricitinib, tofacitinib). In addition to DMARDs, many patients with SRDs may be on systemic corticosteroids including prednisone and dexamethasone. While cost varies by insurance, biologic and targeted synthetic DMARDs tend to cost more (e.g., between $20,000 and $45,000 annually) (1). By comparison, methotrexate, a conventional DMARD, was estimated to cost less than $1,200 annually (1) and corticosteroids may only cost $50 per year. 

DMARDs at the end of life: The decision to stop or change a DMARD at the end of life is complicated and must be individualized. Prognosis, disease activity, route of medication administration, patient preference, hospice enrollment, and cost are common clinical factors involved in these decisions. Collaboration with the patient’s rheumatologist or a clinical pharmacist is highly recommended.  

• Both patients with and without active SRD may benefit from DMARD therapy at the end of life. For patients with active disease, DMARD continuation may be an additional tool for the palliation of pain and minimizing of debility. It also may make sense for patients with well-controlled SRD, especially conventional DMARDs which are more cost effective, to remain on treatment rather than risk flare at the end of life from discontinuation (2). Even for patients with low disease activity (including those on conventional DMARDs), stopping biologics results in flares within 6 months for ~40% of patients (3).
• As patients progress through the end of life, there may be barriers to continued provision of DMARDs. These barriers include patient inability to tolerate oral medications and drug coverage issues from the high cost of biologic and targeted synthetic DMARDs when patients transition to hospice care. Of note, if the SRD is considered related to a patient’s terminal diagnosis, hospice agencies would be required to cover the cost of the DMARD.
• If patients are minimally symptomatic from their SRD, medication de-escalation by stopping a DMARD may be considered based on similar principles proposed for geriatric patients (4). DMARD dosing varies considerably based on the drug involved. In many cases, patients will continue to experience symptomatic benefit for days to months after discontinuation of the DMARD (referred to as a legacy effect) depending on the half-life of the specific DMARD.  This approach may be sensible for patients with a limited prognosis of days to weeks since the common side effect profile of DMARDs (nausea, vomiting, diarrhea, and anorexia) may outweigh any benefit (5). Consultation with a pharmacist or rheumatologist is especially recommended when weighing these factors out. 

Corticosteroids at the end of life: In some patients, it may be reasonable to treat a SRD flare with corticosteroids or even replace a DMARD with daily corticosteroids.  

• The short-term benefit of adding daily corticosteroids often outweighs the long-term side effects for SRD patients with limited prognosis. Corticosteroids may also have additional benefits in relieving non-rheumatologic pain, nausea, and anorexia.
• There is little data to guide appropriate corticosteroid dosing for dying patients with SRD. Starting low and titrating up to effect vs starting high and titrating down to the lowest effective dose depends on the clinical scenario, time involved, prognosis, and risk of flare. Prednisone is widely used as an oral agent by rheumatologists. Prescribed daily doses of prednisone can range up to 100 mg with 40-80 mg being a more common daily dose (6). Methylprednisolone and dexamethasone are common alternatives for patients requiring parenteral dosing.  See Fast Fact #395 for further information on corticosteroid dose equivalency.
• Consultation with a rheumatologist or pharmacist is often helpful in managing corticosteroids for SRD patients at the end of life as well. 

Summary: Clinical challenges often arise for patients with SRDs at the end of life regarding DMARD management. We recommend a multidisciplinary approach that often requires the input of rheumatologists, hospice clinicians, palliative care clinicians, and clinician pharmacists.

References: 

1. Institute for Clinical and Economic Review (ICER), for New England Comparative Effectiveness Public Advisory Council. Targeted immune modulators for rheumatoid arthritis: effectiveness & value. April 2017. URL: https://icer.org/wp-content/uploads/2020/10/NE_CEPAC_RA_Evidence_Report_FINAL_040717.pdf.
2. Ding Q, Shiltz D, Hossami D, et al. The economic burden of biologic disease-modifying antirheumatic drugs in rheumatoid arthritis patients in the United States. Expert review of pharmacoeconomics & outcomes research. 2022 Nov 17;22(8):1231-41.
3. Ghiti Moghadam M, Vonkeman HE, Ten Klooster PM, et al. Stopping tumor necrosis factor inhibitor treatment in patients with established rheumatoid arthritis in remission or with stable low disease activity: a pragmatic multicenter, open‐label randomized controlled trial. Arthritis & rheumatology. 2016 Aug;68(8):1810-7.
4. Lee J, Singh N, Gray SL, et al. Optimizing medication use in older adults with rheumatic musculoskeletal diseases: deprescribing as an approach when less may be more. ACR Open Rheumatology. 2022 Dec;4(12):1031-41.
5. Cho J, Zhou J, Lo D, et al. Palliative and end-of-life care in rheumatology: high symptom prevalence and unmet needs. InSeminars in Arthritis and Rheumatism 2019 Aug 1 (Vol. 49, No. 1, pp. 156-161). WB Saunders.
6. Duru N, Van Der Goes MC, Jacobs JW, et al. EULAR evidence-based and consensus-based recommendations on the management of medium to high-dose glucocorticoid therapy in rheumatic diseases. Annals of the rheumatic diseases. 2013 Dec 1;72(12):1905-13. 

Authors’ Affiliations: Duke University, Durham, NC (MF); Michigan Medicine, Ann Arbor, MI (AM).
Conflicts of Interest: None to report.
Version History: Originally edited by Sean Marks MD; first electronically published in March 2025.